Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs.
Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs.
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DOI：
10.3390/ph6060728
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发表时间：
2013-05-27
期刊：
影响因子：
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通讯作者：
Wang G
中科院分区：
文献类型：
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作者：
Wang G
抗菌肽 (AMP) 是一种小宿主防御蛋白，对于保护植物和动物等多细胞生物免受感染至关重要。自 20 世纪 80 年代以来，每年发现的 AMP 数量稳步增加。来自细菌、原生动物、真菌、植物和动物的 2,000 多种天然 AMP 已注册到抗菌肽数据库 (APD) 中。这些 AMP 中的大多数 (>86%) 具有 11–50 个氨基酸，净电荷为 0 到 +7，疏水百分比在 31–70% 之间。本文总结了基于 APD 的肽发现。主要方法有语言模型、数据库筛选、从头设计和基于模板的设计。使用这些方法，我们鉴定了多种针对 1 型人类免疫缺陷病毒 (HIV-1) 或耐甲氧西林金黄色葡萄球菌 (MRSA) 的有效肽。逐步设计的抗 HIV 肽是二硫键连接的且富含精氨酸，而从头开始设计的抗 MRSA 肽是线性的且富含亮氨酸。因此，抗病毒和抗菌肽有不同的要求，可以通过不同的分子靶点杀死病原体。数据库设计的肽或θ-防御素等天然肽中的氨基酸组成存在偏差，需要使用改进的二维NMR方法进行结构测定，以避免发布误导性的结构和动力学。对于人导管素 LL-37，结构测定需要 3D NMR 技术。 LL-37 的高质量结构为了解其与细菌和其他病原体膜的相互作用提供了坚实的基础。总之，APD 数据库是一个用于存储、分类、搜索、预测和设计针对病原细菌、病毒、真菌、寄生虫和癌细胞的有效肽的综合平台。
Antimicrobial peptides (AMPs), small host defense proteins, are indispensable for the protection of multicellular organisms such as plants and animals from infection. The number of AMPs discovered per year increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been registered into the antimicrobial peptide database (APD). The majority of these AMPs (>86%) possess 11–50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31–70%. This article summarizes peptide discovery on the basis of the APD. The major methods are the linguistic model, database screening, de novo design, and template-based design. Using these methods, we identified various potent peptides against human immunodeficiency virus type 1 (HIV-1) or methicillin-resistant Staphylococcus aureus (MRSA). While the stepwise designed anti-HIV peptide is disulfide-linked and rich in arginines, the ab initio designed anti-MRSA peptide is linear and rich in leucines. Thus, there are different requirements for antiviral and antibacterial peptides, which could kill pathogens via different molecular targets. The biased amino acid composition in the database-designed peptides, or natural peptides such as θ-defensins, requires the use of the improved two-dimensional NMR method for structural determination to avoid the publication of misleading structure and dynamics. In the case of human cathelicidin LL-37, structural determination requires 3D NMR techniques. The high-quality structure of LL-37 provides a solid basis for understanding its interactions with membranes of bacteria and other pathogens. In conclusion, the APD database is a comprehensive platform for storing, classifying, searching, predicting, and designing potent peptides against pathogenic bacteria, viruses, fungi, parasites, and cancer cells.